Nitric oxide (NO) has strong immune suppressive capacities, but the regulation of its activity remains ill defined. NO is produced by Gr-1 cells during immune T cell activation. Our results indicate that superoxide (O₂‾) is produced simultaneously at short range and reduces NO’s suppressive activity. Superoxide dismutase reverses the inactivation of NO by O₂‾.  Interestingly, NO and O₂‾ are produced by distinct immature monocytic and granulocytic cells, respectively, which are distinguishable by Ly-6G expression. IL-23, required for autoimmune inflammation, is involved in the mobilization of both Gr-1 subsets to different degrees, following exposure to mycobacterial products. From these results, a model emerges of an interactive immune regulatory system, named G_reg, consisting of two immature myeloid Gr-1⁺ subsets from distinct lineages. They are mobilized by innate mechanisms involving IL-23, and produce NO or O₂‾ when activated. The degree of NO inactivation by O₂‾ determines the intensity of inflammation.